FAK regulates E-cadherin expression via p-SrcY416/p-ERK1/2/p-Stat3Y705 and PPARγ/miR-125b/Stat3 signaling pathway in B16F10 melanoma cells

// Guoshun Pei 1 , Yan Lan 1 , Dianhua Chen 1 , Lina Ji 1 , Zi-chun Hua 1, 2 1 The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, 210046, China 2 Changzhou High-Tech Research Institute of Nanjing University and Jiangsu Target Pharma Laboratories Inc., Changzhou, Jiangsu, 213164, China Correspondence to: Zi-chun Hua, email: huazc@nju.edu.cn Lina Ji, email: jilina@nju.edu.cn Keywords: FAK, melanoma, miR-125b, E-Cadherin, migration Received: September 09, 2016 Accepted: January 07, 2017 Published: January 17, 2017 ABSTRACT Focal adhesion kinase (FAK) is involved in tumor cell migration and metastasis. However, the underlying mechanism remains unclear. Here, we present a signaling pathway involved in the regulation of melanoma cell migration by FAK. We found that the interference of FAK expression suppressed B16F10 cell migration/metastasis, and altered the expressions of genes involved in melanoma migration/metastasis. The down-regulation of FAK inhibited the expression of p-Src Y416 , p-ERK 1/2 , Stat3 and p-Stat3 Y705 , while promoted the expression of PPARγ, miR-125b and E-cadherin. Then we found that FAK inhibited E-cadherin expression via p-Src Y416 /p-ERK 1/2 / p-Stat3 Y705 and PPARγ/miR-125b/Stat3 signaling pathway in B16F10 cell. Moreover, miR-125b inhibited B16F10 cell migration. Furthermore, we repeated the key data with human melanoma cell line A375. The results obtained from A375 cells fell in line with those from B16F10 cells. Using Oncomine database, we found that the mRNA levels of FAK, Src, ERK 1/2 and Stat3 increased, while the mRNA levels of PPARγ, C21orf34 (miR-125b host gene) and E-cadherin decreased in human metastatic melanoma. The data from human breast cancer confirmed those from metastatic melanoma. Taken together, our study suggests that down-regulation of FAK promotes E-cadherin expression via p-Src Y416 /p-ERK 1/2 /p-Stat3 Y705 and PPARγ/miR-125b/Stat3 signaling pathway. Our findings provide a novel explanation regarding how FAK promotes melanoma cell migration, suggesting that FAK might be a potential target for melanoma therapy.